Polycystic ovary syndrome in Salvador, Brazil: a prevalence study in primary healthcare

Polycystic ovary syndrome (PCOS) is characterized by anovulation, hyperandrogenic symptoms and infertility [1‐3]. PCOS is a hyperinsulinemic syndrome strongly associated with obesity and type 2 diabetes mellitus and has also been associated with high blood pressure, dyslipidemia and cardiovascular disease [2]. It is the most common endocrinopathy in women of reproductive age and is identifiable in early adolescence [4‐6].

PCOS must be diagnosed as early as possible in order to prevent and treat associated conditions and ultimately reduce cardiovascular morbidity and mortality [7, 8]. Nevertheless, the disorder is commonly underdiagnosed, making it impossible to promote preventive measures such as dietary control, physical activity and, whenever required, pharmacological treatment for insulin resistance and associated diseases [9, 10]. The heterogeneity in the clinical signs of PCOS and the lack of uniformity in its defining symptoms hamper diagnosis. In recent years, specialists have attempted to reach a consensus regarding the definition of diagnostic criteria. In 1990, the National Institutes of Health (NIH) established that a diagnosis of PCOS required the simultaneous presence of two clinical criteria: oligoovulation or anovulation and clinical and/or biochemical hyperandrogenism, after all other possible etiologies had been excluded. In 2003, the Rotterdam Consensus (RC), sponsored by the European Society for Human Reproduction and Embryology and the American Society for Reproductive Medicine, stipulated that at least two of the following three criteria should be present: oligoovulation or anovulation, clinical and/or biochemical hyperandrogenism and ultrasonographically detected polycystic ovaries, after the exclusion of all other possible etiologies [11]. The criterion concerning ovarian morphology was added to the initial diagnostic criteria; however, it is absent in 5–20% of cases [10, 12]. The inclusion of phenotypes unrelated to hyperinsulinism remains under debate. Some authors argue that PCOS is a primarily hyperandrogenic condition; therefore, phenotypes that do not include this feature should not be accepted as such [13]. The presence of some of the relevant clinical aspects or all of them appears to be related to a greater or lesser degree to insulin resistance and to the metabolic syndrome [13, 14], which may determine prognosis.

Until a few years ago, the prevalence studies conducted on PCOS were restricted to the United States and some European countries, with reported rates that ranged from 4.6 to 8.0% [6, 14‐18]. This variation may be explained by differences in methodology and in the age-group and ethnicity of the sample populations [19].

Investigators from developing countries with diverse ethnic populations were encouraged to conduct their own evaluations. In July 2008, two studies on the prevalence of PCOS were published simultaneously: a Sri Lankan population-based survey that used the RC criteria to evaluate 2,915 women and reported a prevalence of 6.3% [10], and a Chinese study that evaluated 915 women attending a healthcare unit and reported a prevalence of 2.2% using the NIH criteria [12]. In a Mexican study published in 2010, a prevalence of PCOS of 6.0% was reported in a voluntary population of 150 women in Mexico City [20]. This finding differs from an earlier estimate of 12.8% in Mexican-American women [21]. A recent publication showed an estimated prevalence of 14.6% in Iranian women evaluated in accordance with the Rotterdam criteria [22].

The objective of the present study was to estimate the prevalence of PCOS in Salvador, Brazil. It was expected that the ensuing results would enable clinical protocols to be created to detect the disorder at an early stage at primary healthcare level.

Of all the eligible women screened for the study, 859 were interviewed, yielding a response rate of 96.1%. The mean age of the subjects was 30.7 ± 7.2 years, 88.5% were black (according to the ethnic classifications of the Brazilian Institute of Geography and Statistics) and 62.8% were in a stable marital relationship. The proportion of women in paid employment at the time of the interview was 54.5% (n = 468). Of these, 75.2% (n = 352) earned one minimum wage or less and 95.3% (n = 446) earned a maximum of two minimum wages.

Of all women in the study, 181 (21.1%) were classified as having one (13.6%) or two (5.8%) diagnostic criteria or, alternately, having previously been diagnosed with PCOS despite having no clinical criteria whatsoever (1.6%). These women were then referred to the second phase of the trial (Figure 1) and 107 (59.1%) attended the specialist consultation. Of these, 91.6% underwent hormone evaluation and 57.9% were referred for ultrasonography, with a compliance rate of 90.3%. Of those who failed to attend the specialist visit, 24.7% already had two criteria, thus constituting a diagnosis of PCOS.

A total of 73 women fulfilled the prerequisites for a diagnosis of PCOS according to the RC criteria, resulting in an estimated prevalence of 8.5% (95%CI: 6.80 - 10.56). When the NIH diagnostic criteria were applied, 69 cases of PCOS were found, with a prevalence of 8.03% (95%CI: 6.39 - 10.05). Of the 859 women participating in the study, 84.4% were considered not to have PCOS. In those women with only one criterion who failed to attend the specialist consultation in the second phase of the study or who attended the consultation but failed to complete the evaluation, PCOS was considered undetermined (7.1%) (Figure 1).

When comparing measurements between the three groups of women in whom PCOS was confirmed, undetermined or absent, gradients were found between the groups with respect to all the measurements that attained statistical significance, indicating that there were probably some cases of PCOS in the undetermined group that remained undetected. In the extreme possibility that all the women classified as undetermined actually had PCOS, the maximum prevalence would be 15.6% (95%CI: 13.32 - 18.18).

No statistically significant differences were found between the groups with regard to weight, body mass index, waist circumference, random blood sugar levels or minimum, maximum or mean arterial blood pressure (Table 1). Women with PCOS were younger (p = 0.00), taller (p = 0.04), had fewer children (p = 0.00) and more years of schooling (p = 0.01). Following adjustment for age, the differences in all of these variables remained statistically significant except for height (p = 0.09) (Table 2). With regard to the number of years of schooling, when this variable was categorized into four education levels, there was a clear trend towards a better education level in the group of women diagnosed as having PCOS (p = 0.00) (Table 3). Total testosterone levels were higher in this group (p = 0.01), with a gradient that increased according to the number of criteria present (p = 0.00) (Figure 2). The LH/FSH ratio was also higher in women with PCOS (p = 0.01) and the gradient was similar to that of testosterone with respect to the number of criteria present (p = 0.00) (Figure 3).

The main characteristics of the women screened in the first phase of the study were oligomenorrhea/amenorrhea (54.7%) and hirsutism (59.7%) (Table 4). Likewise, at the end of the study, 78.1% of the 73 participants who had been classified as having PCOS were found to have a combination of these two clinical criteria. Of these, 96.3% had oligomenorrhea and 79.5% had hirsutism. Serum testosterone measurements added another eight cases (11%). Taking acne into consideration for the diagnosis of PCOS and performing ultrasonography in women with only one criterion identified another four cases each (5.5%).

Prevalence rates of 12.6% and 12.9% were found for hirsutism (FG ≥ 6) and for oligomenorrhea/amenorrhea/AUB, respectively. Overall, 18.5% of the women in the study had acne, which was classified as moderate to severe in 2.5% of these cases. In addition, 0.4% of women had androgenic alopecia. PCOS was confirmed in one-third of the women with more severe acne and in two-thirds of those with alopecia.

Of the 126 women who declared in the questionnaire that they had hirsutism and the 196 who stated that they had acne, 108 and 157 women, respectively, had these diagnoses confirmed by the FG score or by dermatological examination (sensitivity of 55.6% and specificity of 91.1% for hirsutism and sensitivity of 51.6% and specificity of 83.4% for acne).

The present results showed a prevalence of PCOS of 8.5% (95%CI: 6.80 - 10.56) in accordance with the Rotterdam criteria in users of the primary public healthcare service in the city of Salvador. When this finding was compared with the prevalence obtained using the NIH criteria (8.03%; 95%CI: 6.39 - 10.05), no statistically significant difference was found, as shown by the overlapping confidence intervals.

Studies conducted in the southern USA [6, 15], Greece [17] and Spain [18] reported prevalence rates of 4.6 - 6.8% using the NIH criteria. The measurements of occurrence were expected to increase between 39% and 50% with the use of the RC, since these criteria may increase the likelihood of diagnosis [29, 30]. The South Asian study conducted in Sri Lanka and the Mexican study reported unexpectedly low prevalence rates of 6.3% and 6.6% (95%CI: 2.3 - 10.9) despite using the RC criteria [10, 20]. In agreement with the Iranian study, the present study showed a higher prevalence, as expected for the criteria that were used [21]. It is important to emphasize that the results found in the various studies would be different if other cut-off points on the FG scale had been used and in this respect the data are not comparable. In the present study, a more sensitive cut-off point (FG ≥ 6) was selected, which led to the identification of a greater number of cases. This was also the choice of most of the nine principal studies on the prevalence of PCOS published to date, in which four used a cut-off point of FG ≥ 6 [6, 12, 15, 17], three used FG ≥ 8 [18, 20, 22] and one used FG ≥ 7 [16]. In the remaining study, self-reported hirsutism was the criterion used [14].

This study included almost all diagnostic possibilities with the exception of the phenotype represented by polycystic ovaries and hyperandrogenemia for which the methodology used for screening was not applicable. To optimize available resources, testosterone measurements and ultrasound scans were not performed in all the women included in the study. It was decided to ignore these possible cases since they are less severe [31] and less common. Their occurrence has been estimated at 0.6% in population-based samples [10] and 5.8% in selected samples [32]. In the present study, the free androgen index was not calculated and for operational reasons progesterone was not measured to confirm anovulation. It was decided that all women reporting oligomenorrhea or amenorrhea would be considered anovulatory [3].

This was the first study conducted in Brazil or South America to estimate the prevalence of PCOS in a random population. The prevalence rate found was 8.5% (95%CI: 6.80 - 10.56). This paper also describes some interesting and unusual findings such as higher stature and a higher education level in these women, which should be addressed in future studies with appropriate designs. The available literature on PCOS emphasizes clinical and physiopathological aspects. Further studies encompassing sociocultural aspects of this syndrome must be carried out, focusing on questions related both to its causality and to its consequences on social trajectories, elements that may enrich the understanding of the phenomenon and its effect on the life of women affected by the syndrome.

Ligia Gabrielli, MD, MPH

Gynecologist, Gynecological Endocrinology Outpatient Clinic, Centro de Diabetes e Endocrinologia da Bahia.

Investigator, Institute of Collective Health, Federal University of Bahia, Brazil.

Estela Maria Leão de Aquino, MD, MPH, DrPH

Professor of Epidemiology; Methods for Health Research; Gender, Sexuality and Reproductive Health at the Institute of Collective Health, Federal University of Bahia, Brazil.